Haemostasis Unit, Department of Haematology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
Department of Natural Sciences, Faculty of Science and Technology, Middlesex University, London, United Kingdom.
Semin Thromb Hemost. 2022 Sep;48(6):643-660. doi: 10.1055/s-0042-1744363. Epub 2022 Jun 1.
Lupus anticoagulant (LA) is one of the three criteria antiphospholipid antibodies (aPLs) employed in classification, and by default diagnosis, of antiphospholipid syndrome (APS). Detection of LA is not via calibrated assays but is based on functional behavior of the antibodies in a medley of coagulation assays. A prolonged clotting time in a screening test is followed by demonstration of phospholipid dependence and inhibitory properties in confirmatory and mixing tests, respectively, which are modifications of the parent screening test. Complications arise because no single screening test is sensitive to every LA, and no test is specific for LA, because they are prone to interference by other causes of elevated clotting times. Several screening tests are available but the pairing of dilute Russell's viper venom time (dRVVT) with LA-sensitive activated partial thromboplastin time (aPTT) is widely used and recommended because it is proven to have good detection rates. Nonetheless, judicious use of other assays can improve diagnostic performance, such as dilute prothrombin time to find LA unreactive with dRVVT and aPTT, and the recently validated Taipan snake venom time with ecarin time confirmatory test that are unaffected by vitamin K antagonist and direct factor Xa inhibitor anticoagulation. Expert body guidelines and their updates have improved harmonization of laboratory practices, although some issues continue to attract debate, such as the place of mixing tests in the medley hierarchy, and areas of data manipulation such as assay cut-offs and ratio generation. This article reviews current practices and challenges in the laboratory detection of LA.
狼疮抗凝物 (LA) 是抗磷脂抗体 (aPL) 三种分类标准之一,默认情况下也是抗磷脂综合征 (APS) 的诊断标准。LA 的检测不是通过校准的检测方法,而是基于抗体在一系列凝血检测中的功能行为。在筛选检测中出现凝血时间延长后,分别在确认和混合检测中显示出磷脂依赖性和抑制性特征,这两种检测方法都是对原始筛选检测的修改。由于没有单一的筛选检测对所有 LA 都敏感,也没有检测方法对 LA 具有特异性,因为它们容易受到其他导致凝血时间延长的原因的干扰,因此会出现并发症。有几种筛选检测方法,但稀释蝰蛇毒时间 (dRVVT) 与 LA 敏感的活化部分凝血活酶时间 (aPTT) 的配对被广泛使用和推荐,因为它已被证明具有良好的检测率。尽管如此,明智地使用其他检测方法可以提高诊断性能,例如稀释的凝血酶原时间可以发现与 dRVVT 和 aPTT 无反应的 LA,以及最近验证的 taipan 蛇毒时间与 ecarin 时间确认检测,它们不受维生素 K 拮抗剂和直接因子 Xa 抑制剂抗凝的影响。专家机构指南及其更新改善了实验室实践的协调,但一些问题仍在继续引起争议,例如混合检测在检测方法中的地位,以及检测方法的界限和比值生成等数据处理领域。本文回顾了 LA 实验室检测的当前实践和挑战。